Effect of 0.01%, 0.02% and 0.04% Atropine eyedrops vs Placebo on myopia incidence in pre-myopic children: A randomized clinical trial.

PURPOSE: To investigate the dose-response relationship and individual efficacy of 0.01%, 0.02%, and 0.04% atropine eye drops for preventing myopia onset in pre-myopic children.

DESIGN

Twelve-month randomized, placebo-controlled, double-blind clinical trial conducted in Shanghai primary schools (March 2023-December 2024).

METHODS

Children aged 6-10 years with cycloplegic spherical equivalent refraction of -0.50 to +0.75 diopters (D) were randomized 1:1:1:1 to placebo or 0.01%, 0.02%, or 0.04% atropine once daily. Primary outcome was 12-month cumulative myopia incidence (SER ≤ -0.50 D in the worse eye); secondary outcomes were changes in SER and axial length of the worse eye. Children with ocular or systemic diseases, prior orthokeratology use, or other myopia control interventions were excluded.

RESULTS

Among the 428 randomized children, 395 (92.3%) were included in the final primary analysis. Cumulative myopia incidence was 39.0%, 29.4%, 26.9%, and 25.8% in the control, 0.01%, 0.02%, and 0.04% groups, respectively (Ptrend = 0.044). SER changes showed a significant dose-response relationship (Ptrend < 0.001), while no significant dose-response was observed for axial length (Ptrend = 0.418). Compared with control, the 0.04% atropine group showed a significantly lower mean change in SER (P < 0.001). Subgroup analyses revealed more pronounced efficacy in children aged 8-10 years, where all concentrations significantly reduced myopia incidence and SER progression. No significant differences in adverse event incidence were observed between groups.

CONCLUSIONS

Low-concentration atropine demonstrated a dose-response relationship for reducing cumulative myopia incidence and slowing refractive progression in pre-myopic children, but no such relationship on axial length. This preliminary evidence suggests potential for early myopia prevention, but larger, longer-term trials are needed before recommending an optimal clinical concentration.